This proposal focuses on topic 17. Basic Underlying Mechanisms of Musculoskeletal Aging. The long term objectives of this project are to better understand, and thus prevent or correct dibilitating age related conditions in bone such as osteoporosis. The disease process, as well as preventive or corrective therapy, directly affects bone structure through modulated cellular activity. The trabecular structure of cancellous, or spongy, bone is most dramatically affected by disease. In osteoporosis, trabecular thinning and decreased connectivity leads to spontaneous fractures in the vertebrae and hips. Imaging techniques such as micro computed tomography (micro-CT) allow visualization and analysis of the trabecular microarchitecture. When the volume of trabecular bone is sufficiently large, micromechanical finite element analysis (micro-FEA) can also be done to nondestructively test the mechanical behavior and predict the strength of trabecular bone. Proposed herein is a unique experimental model, using rabbits instead of rats, that will monitor the changing trabecular microarchitecture and micromechanical environment in live animals. The specific aims are: 1) to develop a reliable and repeatable technique for obtaining three-dimensionally reconstructed micro-CT images of the trabecular bone in the distal femur of live rabbits; and 2) to evaluate and compare distal femoral trabecular microarchitectural changes by studying the same bone through time during aging of normal and ovariectomized rabbits. A custom designed micro-CT system will support a live rabbit while allowing an isolated hind limb to be imaged in three dimensions at high resolution. The technique will be validated by comparison with a proven method for obtaining high resolution three-dimensional images. Next, groups of intact and ovariectomized rabbits will be scanned four times over twelve weeks so that changes in specific microstructural characteristics can be monitored and compared. Unscanned control rabbits will also be evaluated at twelve weeks to determine whether there are any adverse effects from radiation exposure. This model will make it possible to investigate the natural history of bone disease at the microarchitectural level and to monitor bone strength. It will give investigators the opportunity to watch the specific trabecular surfaces that are affected by various treatments and to observe when these effects occur.